Yalcin Ozlem, Ulker Pinar, Yavuzer Ugur, Meiselman Herbert J, Baskurt Oguz K
Department of Physiology, Akdeniz University Faculty of Medicine, Antalya, Turkey.
Am J Physiol Heart Circ Physiol. 2008 May;294(5):H2098-105. doi: 10.1152/ajpheart.00015.2008. Epub 2008 Mar 7.
Endothelial function is modulated by wall shear stress acting on the vessel wall, which is determined by fluid velocity and the local viscosity near the vessel wall. Red blood cell (RBC) aggregation may affect the local viscosity by favoring axial migration. The aim of this study was to investigate the role of RBC aggregation, with or without altered plasma viscosity, in the mechanically induced nitric oxide (NO)-related mechanisms of endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultured on the inner surface of cylindrical glass capillaries that were perfused with RBC suspensions having normal and increased aggregation at a nominal shear stress of 15 dyn/cm(2). RBC aggregation was enhanced by two different approaches: 1) poloxamer-coated RBC suspended in normal, autologous plasma, resulting in enhanced aggregation but unchanged plasma viscosity and 2) normal RBC suspended in autologous plasma containing 0.5% dextran (mol mass 500 kDa), with a similar level of RBC aggregation but higher plasma viscosity. Compared with normal cells in unmodified plasma, perfusion with suspensions of poloxamer-coated RBC in normal plasma resulted in decreased levels of NO metabolites and serine 1177 phosphorylation of endothelial nitric oxide synthase (eNOS). Perfusion with normal RBC in plasma containing dextran resulted in a NO level that remained elevated, whereas only a modest decrease of phosphorylated eNOS level was observed. The results of this study suggest that increases of RBC aggregation tendency affect endothelial cell functions by altering local blood composition, especially if the alterations of RBC aggregation are due to modified cellular properties and not to plasma composition changes.
内皮功能受作用于血管壁的壁面剪切应力调节，壁面剪切应力由流体速度和血管壁附近的局部粘度决定。红细胞（RBC）聚集可能通过促进轴向迁移来影响局部粘度。本研究的目的是探讨红细胞聚集在有或无血浆粘度改变情况下，在机械诱导的内皮细胞一氧化氮（NO）相关机制中的作用。人脐静脉内皮细胞（HUVEC）培养在圆柱形玻璃毛细管的内表面，毛细管中灌注具有正常聚集性和聚集性增加的红细胞悬液，名义剪切应力为15达因/厘米²。通过两种不同方法增强红细胞聚集：1）泊洛沙姆包被的红细胞悬浮于正常自体血浆中，导致聚集增强但血浆粘度不变；2）正常红细胞悬浮于含0.5%葡聚糖（分子量500 kDa）的自体血浆中，红细胞聚集水平相似但血浆粘度更高。与未修饰血浆中的正常细胞相比，用泊洛沙姆包被的红细胞悬液灌注正常血浆导致NO代谢产物水平降低以及内皮型一氧化氮合酶（eNOS）丝氨酸1177磷酸化水平降低。用含葡聚糖的血浆中的正常红细胞灌注导致NO水平持续升高，而仅观察到磷酸化eNOS水平适度降低。本研究结果表明，红细胞聚集倾向增加通过改变局部血液成分影响内皮细胞功能，特别是当红细胞聚集的改变是由于细胞特性改变而非血浆成分变化时。
